Effects of l-Triiodothyronine and the Thyromimetic L-94901 on Serum Lipoprotein Levels and Hepatic Low-Density Lipoprotein Receptor, 3-Hydroxy-3-methylglutaryl Coenzyme A Reductase, and Apo A-I Gene Expression》.pdf

Biochemical Pharmacology, Vol. 56, pp. 121–129, 1998. ISSN 0006-2952/98/$19.00 0.00 © 1998 Elsevier Science Inc. All rights reserved. PII S0006-2952(98)00119-1 Effects of L-Triiodothyronine and the Thyromimetic L-94901 on Serum Lipoprotein Levels and Hepatic Low-Density Lipoprotein Receptor, 3-Hydroxy-3- methylglutaryl Coenzyme A Reductase, and Apo A-I Gene Expression Gene C. Ness,*‡ Dayami Lopez,* Christopher M. Chambers,* William P. Newsome,† Peter Cornelius,† Catherine A. Long‡ and H. James Harwood, Jr.† *DEPARTMENT OF BIOCHEMISTRY AND MOLECULAR BIOLOGY, COLLEGE OF MEDICINE AND THE INSTITUTE FOR BIOMOLECULAR SCIENCE, UNIVERSITY OF SOUTH FLORIDA, TAMPA, FL 33612; AND †DEPARTMENT OF METABOLIC DISEASES, PFIZER CENTRAL RESEARCH, GROTON, CT 06340, U.S.A. ABSTRACT. The mechanisms by which thyroid hormone (triiodothyronine (T )) and a thyromimetic, 3 2-amino-3-(3,5-dibromo-4-[4-hydroxy-3-(6-oxo-1,6-dihydro-pyridazin-3-ylmethyl)-phenoxyl]-phenyl)- propionic acid (L-94901), lower plasma low density lipoprotein (LDL) cholesterol and raise plasma high density lipoprotein (HDL) cholesterol levels was investigated in thyroidectomized and sham-operated rats. Thyroidec- tomy resulted in a 77% increase in plasma LDL cholesterol, a 60% decrease in plasma triglycerides, and a modest reduction in